Since 1980, retroviruses have been linked to the pathogenesis of several infectious and malignant diseases in man, including Adult T-cell leukemia and Acquired Immunodeficiency Syndrome (AIDS). We have recently reported the presence of antibodies reactive with purified HTLV-III/LAV, but not HTLV-I, in native populations in Venezuela not at risk for AIDS, including aboriginal Amazonian Indians, other inhabitants of rural in land areas, and patients with malaria and Chagas' disease. Attempts to culture virus from lymphocytes of some of these subjects have revealed the presence of a retrovirus related to, but distinct from, the American isolate of HTLV-III/LAv. Since AIDS is rare in Venezuela, we hypothesize that: a) this might be a new member of the family of human retroviruses; b) the virus(es) might be an ancestor of AIDS-associated retrovirus; c) the natural history of HTLV-III/LAV-type virus infection might change upon transmission into different environment. We propose to characterize the indigenous HTLV-III/LAV-type retrovirus from South America (SA-RV) and to compare it with HTLV-I and the immuno-destructive AIDS retrovirus. Specifically, we propose to complete the ongoing seroepidemiological survey of Venezuelan populations to determine the prevalence and endemic areas of the virus. We will isolate, purify and clone virus from representative groups, including Amazonian Indians and patients with malaria or Chagas' diseases. We will compare the physical, morphological and biochemical characteristics, genome structure and organization, host cell range and biological activity of these viruses with those of the HTLV-I and the U.S. isolate of HTLV-III/LAV. Serum and blood samples for the initial stages of this study will be provided by Dr. Merino. Viral antibodies and antigens will be tested in our laboratory by ELISA, immunofluorescence, radioimmunoprecipitation and Western blotting. Virus will be isolated by co-cultivation with acceptor CEM or DC-10 cells. Standard molecular-biological techniques will be used for genome detection, analysis, cloning and sequencing. The studies will shed light on the biology and pathogenicity of HTLV-III/LAV or similar retroviruses existing under AIDS endemic and non-endemic conditions. This could have important implications for AIDS prevention and therapy, as well as might contribute to the understanding of etiology and pathogenesis of other diseases.